chr1-160841488-G-A

Position:

• chr1-160841488-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000368033.7(CD244):​c.392C>T​(p.Pro131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P131S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD244 ENST00000368033.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.631

Genes affected

CD244 (HGNC:18171): (CD244 molecule) This gene encodes a cell surface receptor expressed on natural killer (NK) cells (and some T cells) that mediate non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070676535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD244	NM_016382.4	c.380-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368034.9	NP_057466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD244	ENST00000368033.7	c.392C>T	p.Pro131Leu	missense_variant	3/9	1		ENSP00000357012	A2
CD244	ENST00000368034.9	c.380-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016382.4	ENSP00000357013	P2
CD244	ENST00000322302.7	c.379+96C>T		intron_variant		1		ENSP00000313619
CD244	ENST00000492063.5	c.380-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2		ENSP00000432636

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2022

The c.392C>T (p.P131L) alteration is located in exon 3 (coding exon 3) of the CD244 gene. This alteration results from a C to T substitution at nucleotide position 392, causing the proline (P) at amino acid position 131 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.27
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.14	B
Vest4		0.13
MutPred		0.44		Loss of disorder (P = 0.0445);
MVP		0.31
MPC		0.071
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.057
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160811278;